This application responds to a request for proposals issued by the National Cancer Institute that asked for planning efforts that would result in an integrated research proposal to identify how nutrients modulate genetic and epigenetic pathways that are involved with cancer. We will develop an integrated plan to examine how nutrients modulate a series of related processes that mediate the genetic pathways involved in reactive oxygen mitogen production and DNA damage, mechanisms for repair of DNA, and the consequences of damage to DNA on genetic pathways that regulate cell cycling and elimination of damaged cells by apoptosis. This application is a logical extension of a group of already strong individual research programs that benefit from an integrated effort to enhance the cross-disciplinary character of the research. The cadre of investigators committed to this initial planning phase, along with many additional faculty members at UNC, is arguably one of the strongest groups in the world and bring innovative hypotheses and advanced methods to address the role of nutrition and genetic pathways in cancer pathophysiology. The basic premise of the current application is that nutrients interact in a specific manner to modulate various steps in the genetic and epigenetic pathways that mediate how oxidant stress causes cancer. Specifically: 1. Nutrients modulate how free radicals are generated and whether they survive to: (a) damage DNA; (b) activate signaling cascades involved in neoplastic transformation (mitogens, kinases, transcription factors, etc.), 2. Nutrients modify whether DNA is repaired or escapes repair, 3. Nutrients modify how DNA damage effects the genetic pathways and related signals that regulate cell cycling, 4. Nutrients modify how DNA damage effects the genetic pathways and related signals that regulate cell cycling, 5. Genetic polymorphisms exist which influence how nutrients interact with each of the above steps. The proposal will be enriched by continual interaction with experts and possible future collaborators from UNC-CH, the Research Triangle Park, as well as from other distinguished domestic and foreign academic and governmental institutions.